Repair-associated macrophages increase after early-phase microglia attenuation to promote ischemic stroke recovery

作者：Xiaotao Zhang, Huaming Li, Yichen Gu, An Ping, Jiarui Chen, Zhang Qia, Zhouhan Xu, Jijun Wang, Shenjie Tang, Rui Wang, Jianan Lü, Liqin Lu, Cheng‐Hao Jin, Ziyang Jin, Jianmin Zhang, Ligen Shi · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-58254-y · 被引用次数：46 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Immune cells in cancer、Neurological Disease Mechanisms and Treatments

Ischemic stroke recovery involves dynamic interactions between the central nervous system and infiltrating immune cells. Peripheral immune cells compete with resident microglia for spatial niches in the brain, but how modulating this balance affects recovery remains unclear. Here, we use PLX5622 to create spatial niches for peripheral immune cells, altering the competition between infiltrating immune cells and resident microglia in male mice following transient middle cerebral artery occlusion (tMCAO). We find that early-phase microglia attenuation promotes long-term functional recovery. This intervention amplifies a subset of monocyte-derived macrophages (RAMf) with reparative properties, characterized by high expression of GPNMB and CD63, enhanced lipid metabolism, and pro-angiogenic activity. Transplantation of RAMf into stroke-affected mice improves white matter integrity and vascular repair. We identify Mafb as the transcription factor regulating the reparative phenotype of RAMf. These findings highlight strategies to optimize immune cell dynamics for post-stroke rehabilitation. Recovery from ischemic stroke involves dynamic interactions between immune cells and the brain. Here, the authors show that microglia reduction promotes long-term stroke recovery in mice by expanding reparative macrophages, enhancing vascular repair and white matter integrity.